Gustatory sense is an important sense for life. Thus, abnormal gustatory sense gives a strong stress to patients' mentality. However, since such gustatory sense is a subjective sense, which can be recognized by only a person in question, it is difficult to objectively grasp the pathologic condition thereof. Hence, it is hard to say that an effective treatment is carried out for patients suffering from dysgeusia. Moreover, since such disorder of the sense of taste is not directly associated with the life-or-death matter of humans, it hardly becomes the object of interest for researchers. To date, dysgeusia has been tested by two main types of methods. One of them is called electrogustometry. This is a method, which comprises passing a weak current through the tongue and determining the disorder of the sense of taste based on the degree of the feeling obtained when electrical stimulation that is similar to taste is given. However, it is difficult for this method to detect abnormalities of individual qualities of tastes such as sweetness or bitterness. The other method is called a filter disk method. The filter disk method comprises placing a filter impregnated with each of taste substances in various concentrations on various sites of the tongue and hearing opinions from the subjects regarding the presence or absence of the taste. This method enables detection of the degree of feeling of 4 basic tastes such as sweetness, saltiness, sourness and bitterness, or the correctness of the feeling. However, this method is problematic in that good results cannot be obtained if subjects do not reach age when they understand the concept of this test, or if they do not have enough knowledge. Moreover, this method is also problematic when subjects do not know how to express the taste although they feel the taste. Thus, in a case where such subjects are infants and toddlers, or are elder people who are hearing-impaired, this test has almost no sense.
The aforementioned method enables detection of the presence or absence of dysgeusia, but it cannot clarify the cause of such dysgeusia.
By the way, in the case of mammals, the sense of taste is considered to be classified into 5 types of tastes such as sweetness, bitterness, delicious taste, sourness, and saltiness. Each quality of taste is considered to be transmitted via each different communication system. It is said that G protein-coupled receptors (GPCR) are involved in transmission of sweetness, bitterness, and delicious taste, and that ion channels are deeply involved in transmission of saltiness and sourness. However, the relationship between such receptors and taste substances has not yet been clarified. If such gustatory receptors (GPCR or channel proteins) selectively activate or inactivate towards chemical stimulation from the outside world, it is considered that cells on the tongue (taste cells) that express such receptors respond to such stimulation, and that information regarding a taste substance is transmitted to the central nerve.
As stated above, several gustatory receptors belong to the G protein-coupled receptors having a seven-transmembrane structure. In recent years, studies regarding G protein-coupled receptors for taste substances have vigorously been progressing. At current, T1R, T2R, and THTR families have been identified as gustatory receptors (Takeda et al. FEBS Lett. 520, 97-101, 2002) (National Publication (in Japan) of International Patent Application Nos. 2003-530098 and 2003-510037). However, the type of a substance used as a ligand (agonist) of such receptors, and in particular, of the THTR family, is still unknown.
Accordingly, it is desired to clarify such gustatory receptors, and to find a ligand acting as a taste substance. In addition, it is also desired to develop a novel method for testing dysgeusia, which does not depend on the personal view of a subject.